Abstract Breathing exercises, alone or as a component of mind-body interventions such as meditation and yoga, have potential for amelioration of a wide range of acute and chronic disorders. The present proposal describes the application of a new translational tool for ambulatory monitoring of breathing to the investigation of the effects of a specific breathing exercise, mindful breathing (MB), on a major cardiovascular risk factor, blood pressure (BP). The new monitor enables continuous measurement, not only of breathing rate, but of CO2 in expired air (PetCO2) in the natural environment, as well as the clinic setting. The relevance of PetCO2 is that it co-varies with blood CO2, which in turn regulates acid- base balance, known to be vital for stable physiological function in all bodily tissues, and thus important to health. The present project proposes a study of MB effects on PetCO2, breathing rate, and BP in individuals with prehypertension. A first specific aim is to test the hypothesis that an eight week program of MB will produce greater changes in PetCO2 than occur in a health education (HE) attention control group. A second specific aim is to test the hypothesis that MB will produce greater reductions in 24-hr BP levels than HE, and that MB participants with greater decreases in BP will show larger changes in PetCO2 than those with smaller BP changes. The new monitor has the capacity to provide feedback to participants when an acute change in breathing that alters PetCO2 has occurred. The third specific aim of this project is, therefore, to investigate the effect of supplementing MB and HE training with PetCO2 feedback on BP during a 3-month follow-up period. This project has the potential to elucidate a mechanism by which MB or other mind-body interventions can influence a major risk factor for cardiovascular disease, and thereby demonstrate the applicability of this new translational tool to research in CAM.